Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Prevalence of SARS-CoV-2-specific antibodies in a sample of the Lithuanian population-based study in Spring 2023.

Objectives: Despite positive trends in SARS-CoV-2 epidemiology, seroprevalence surveys remain an important tool for estimating the magnitude of the COVID-19 pandemic. This study aimed to investigate the prevalence of IgG antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) proteins in a sample of the Lithuanian population (N = 517) and evaluate how the pattern of seropositivity correlates with the levels of SARS-CoV-2 infection and vaccination. Methods: Study participants (aged 18-88 years) filled in the questionnaire self-reporting their demographic-social variables, health status, and SARS-CoV-2-related status. The anti-S and anti-N IgG levels were estimated using a microarray ELISA test. Results: After several pandemic waves and vaccination campaign, the seroprevalence of SARS-CoV-2-specific IgG in the analyzed sample was 97.87 % by March-May 2023. We determined the 96.91 % prevalence of anti-S and 58.03 % prevalence of anti-N IgG. The majority of study participants (71.18 %) had hybrid immunity induced by vaccination and SARS-CoV-2 infection. 20.3 % of study participants were anti-N IgG positive without reporting any previous symptoms or a positive SARS-CoV-2 test. A decline of anti-N IgG positivity within 9 months after infection was observed. Conclusions: This study demonstrates high total seroprevalence in March-May 2023 in all age groups indicating a widely established humoral immunity against SARS-CoV-2 in Lithuania.

Plasma of COVID-19 Patients Does Not Alter Electrical Resistance of Human Endothelial Blood-Brain Barrier In Vitro.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study, we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon γ-induced protein 10 kDa, hepatocyte growth factor, and interleukin-18 in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not affect BBB paracellular pathway directly and suggest that pathological remodeling (if any) of BBB during COVID-19 may occur through indirect or yet unknown mechanisms.

Characteristics of COVID-19 Disease in Renal Transplant Recipients.

Background and Objectives: Kidney transplant recipients are at risk of developing more severe forms of COVID-19 infection. The aim of this study was to compare the clinical course of COVID-19 infection among kidney transplant patients and a control group. Materials and Methods: We examined 150 patients hospitalized with COVID-19 infection. Patients were divided into study (kidney transplant recipients, n = 53) and control (without a history of kidney transplantation, n = 97) groups. Demographics, clinical characteristics, treatment data, and clinical outcomes were assessed. Results: The median patient age was 56.0 (46.0-64.0) years, and seventy-seven patients (51.3%) were men. The median Charlson comorbidity index was higher in the study group (3.0 vs. 2.0, p < 0.001). There was a higher incidence of hypoxemia in the control group upon arrival (52.6% vs. 22.6%, p = 0.001) and a higher NEWS index median (2.0 vs. 1.0 points, p = 0.009) and incidence of pneumonia during hospitalization (88.7% vs. 73.6%, p = 0.023). In the study group, there were more cases of mild (26.4% vs. 11.3%, p = 0.023) and critically severe forms of COVID-19 infection (26.4% vs. 3.1%, p < 0.001), kidney failure was more prevalent (34.0% vs. 1.0%, p < 0.001), and a greater number of patients were transferred to the intensive care unit (22.6% vs. 3.1%, p < 0.001) and died (18.9% vs. 1.0%, p < 0.001). Multivariable analysis revealed that treatment in the intensive care unit correlated with a higher mortality rate than transplantation itself (HR = 20.71, 95% CI 2.01-213.33, p = 0.011). Conclusions: The course of the COVID-19 disease in kidney transplant recipients is heterogeneous and can be more severe than in the general population. Even though patients may be hospitalized with fewer symptoms, complications and death are more likely to occur.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

The Challenges of Vaccine Trial Participation among Underserved and Hard-to-Reach Communities: An Internal Expert Consultation of the VACCELERATE Consortium.

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Clinical characteristics and predictors for in-hospital mortality in adult COVID-19 patients: A retrospective single center cohort study in Vilnius, Lithuania.

BACKGROUND: The COVID-19 infection had spread worldwide causing many deaths. Mortality rates and patients' characteristics varied within and between countries, making it important to understand the peculiarities of different populations. The aim of this study was to identify the main predictors associated with in-hospital mortality due to COVID-19 in Vilnius, Lithuania. MATERIALS AND METHODS: This was a retrospective observational cohort study conducted at Vilnius University Hospital Santaros Clinics, Lithuania. The study included SARS-CoV-2 positive patients aged over 18 years and hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. The predictive values of laboratory parameters were evaluated using ROC analysis. Multivariable binary logistic regression was performed to reveal predictors of in-hospital mortality due to COVID-19. RESULTS: Among 2794 patients, 54.4% were male, the age median was 59 years (IQR 48-70), 47.4% had at least one comorbidity. The most common comorbidities were arterial hypertension (36.9%) and diabetes mellitus (13.7%). Overall, 12.7% of patients died. Multivariable regression revealed that age (OR 1.04, 95%CI 1.02-1.06), congestive heart failure (OR 3.06, 95%CI 1.96-4.77), obesity (OR 3.90, 95%CI 2.12-7.16), COPD (OR 2.92, 95%CI 1.12-7.60), previous stroke (OR 5.80, 95%CI 2.07-16.21), urea >7.01 mmol/l (OR 2.32, 95%CI 1.47-3.67), AST/ALT >1.49 (OR 1.54, 95%CI 1.08-2.21), LDH >452.5 U/l (OR 2.60, 95%CI 1.74-3.88), CRP >92.68 mg/l (OR 1.58, 95%CI 1.06-2.35), IL-6 >69.55 ng/l (OR 1.62, 95%CI 1.10-2.40), and troponin I >18.95 ng/l (OR 2.04, 95%CI 1.38-3.02), were associated with increased risk for in-hospital mortality in COVID-19 patients. CONCLUSIONS: Age, congestive heart failure, obesity, COPD, prior stroke, and increased concentration of urea, LDH, CRP, IL-6, troponin I, ALT to AST ratio were identified to be the predictors for in-hospital mortality of COVID-19 patients.

The Association between COVID-19 Infection and Kidney Damage in a Regional University Hospital.

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman's correlation coefficient = -0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die.

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe.

BACKGROUND: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.

SARS-CoV-2 RT-qPCR Ct values in saliva and nasopharyngeal swab samples for disease severity prediction.

Background: Comparison of clinical value of RT-qPCR-based SARS-CoV-2 tests performed on saliva samples (SSs) and nasopharyngeal swab samples (NPSs) for prediction of the COVID-19 disease severity. Methods: Three paired SSs and NPSs collected every 3 days from 100 hospitalised COVID-19 patients during 2020 Jul-2021 Jan were tested by RT-qPCR for the original SARS-CoV-2 virus and compared to 150 healthy controls. Cases were divided into mild+moderate (Cohort I, N = 47) and severe disease (Cohort II, N = 53) cohorts and compared. Results: SARS-CoV-2 was detected in 65% (91/140) vs. 53% (82/156) of NPSs and 49% (68/139) vs. 48% (75/157) of SSs collected from Cohort I and II, respectively, resulting in the total respective detection rates of 58% (173/296) vs. 48% (143/296) (P = 0.017). Ct values of SSs were lower than those of NPSs (mean Ct = 28.01 vs. 30.07, P = 0.002). Although Ct values of the first SSs were significantly lower in Cohort I than in Cohort II (P = 0.04), it became negative earlier (mean 11.7 vs. 14.8 days, P = 0.005). Multivariate Cox proportional hazards regression analysis showed that Ct value ≤30 from SSs was the independent predictor for severe COVID-19 (HR = 10.06, 95% CI: 1.84-55.14, P = 0.008). Conclusion: Salivary RT-qPCR testing is suitable for SARS-CoV-2 infection control, while simple measurement of Ct values can assist in prediction of COVID-19 severity.

Influenza vaccine effectiveness in patients hospitalized with severe acute respiratory infection in Lithuania during the 2019-2020 influenza season: a test negative case - control study.

BACKGROUND: Influenza is a contagious viral airborne disease that adds to the clinical and economic burden on the healthcare system. It could be prevented substantially by seasonal influenza vaccination. Seasonal influenza vaccine effectiveness (SIVE) varies a lot and should therefore be monitored. This report aims to update age-stratified SIVE estimates among patients hospitalized due to severe acute respiratory infection (SARI) during the 2019-2020 influenza season. METHODS: We performed a test-negative case-control study between December 2019 and April 2020 influenza season. We estimated SIVE and its 95% confidence intervals (95% CI) with logistic regression as (1-odds ratio)*100%. The models were adjusted for covariates that changed the unadjusted SIVE by ≥ 10%. RESULTS: Among 84 participants, 32 (38.1%) were influenza positive, mostly with A(H1N1)pdm09 (25 cases; 78.1%). SIVE against any influenza adjusted for age and heart disease was 39.2% (95% CI: -119.3%, 83.1%). Age-stratified point estimates adjusted for heart diseases indicated different SIVE, and were 64.0% (95% CI: -309.2%, 96.8%) and 21.6% (95% CI: -252.2%, 82.6%) for 18-64 and ≥ 65 year-old participants, respectively. CONCLUSIONS: The point estimates suggested low to moderate SIVE against any influenza among hospitalized 18-64-year-old SARI participants, while low estimates were found in the ≥ 65-year-old group. Although broad SIVE confidence intervals indicate a small sample size and therefore the results can serve only as indicatory, they are in line with the estimates reported by other studies during the 2019-2020 season.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials.

The Quality of Life in Surgically Treated Head and Neck Basal Cell Carcinoma Patients: A Comprehensive Review.

In this review, we examine current literature analyzing the impact of surgical treatment on the QoL in patients with head and neck BCC. A comprehensive literature review was performed using the main databases. As many as six out of 322 articles were selected for the final analysis. The selected articles were published in the period between 2004 and 2021, most published within the last two years. All analyzed studies were prospective. Five out of six studies evaluated NMSC consisting of both BCC and SCC, and only one study selectively evaluated the impact of surgical treatment on QoL in patients with craniofacial BCC. Authors of the selected studies reported that QoL improves following the surgery; however, the effect on QoL varies. Patients' age, gender, marital status, education level, and employment status had a stronger correlation with QoL postoperatively, especially during the late follow-up period. Younger patients were more bothered by appearance-related issues. One study concluded that elderly patients did not experience a statistically significant improvement in QoL. This literature review demonstrated that there is no clear consensus on the use of a single disease-specific QoL measurement tool. Furthermore, there is a lack of studies assessing the impact of surgical treatment on QoL exclusively in patients with head and neck BCC and studies analyzing the multivariate correlation between QoL and tumor type, size, anatomic site, and treatment outcomes.

Hyperglycaemia and Its Prognostic Value in Patients with COVID-19 Admitted to the Hospital in Lithuania.

BACKGROUND AND OBJECTIVES: Increased blood glucose levels atadmission are frequently observed in COVID-19 patients, even in those without pre-existing diabetes. Hyperglycaemia is associated with an increased incidence of severe COVID-19 infection. The aim of this study was to evaluate the association between hyperglycaemia at admission with the need for invasive mechanical ventilation (IMV) and in-hospital mortality in patients without diabetes who were hospitalized for COVID-19 infection. MATERIALS AND METHODS: This retrospective observational study was conducted at Vilnius University Hospital Santaros Clinics, Lithuania with adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 and were hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. Based on blood glucose levels on the day of admission, patients without diabetes were divided into 4 groups: patients with hypoglycaemia (blood glucose below 4.0 mmol/L), patients with normoglycaemia (blood glucose between ≥4.0 mmol/L and <6.1 mmol/L), patients with mild hyperglycaemia (blood glucose between ≥6.1 mmol/L and <7.8 mmol/L), and patients with intermittent hyperglycaemia (blood glucose levels ≥7.8 mmol/L and <11.1 mmol/L). A multivariable binary logistic regression model was created to determine the association between hyperglycaemia and the need for IMV. Survival analysis was performed to assess the effect of hyperglycaemia on outcome within 30 days of hospitalization. RESULTS: Among 1945 patients without diabetes at admission, 1078 (55.4%) had normal glucose levels, 651 (33.5%) had mild hyperglycaemia, 196 (10.1%) had intermittent hyperglycaemia, and 20 (1.0%) had hypoglycaemia. The oddsratio (OR) for IMV in patients with intermittent hyperglycaemia was 4.82 (95% CI 2.70-8.61, p < 0.001), and the OR was 2.00 (95% CI 1.21-3.31, p = 0.007) in those with mild hyperglycaemia compared to patients presenting normal glucose levels. The hazardratio (HR) for 30-day in-hospital mortality in patients with mild hyperglycaemia was 1.62 (95% CI 1.10-2.39, p = 0.015), while the HR was 3.04 (95% CI 2.01-4.60, p < 0.001) in patients with intermittent hyperglycaemia compared to those with normoglycaemia at admission. CONCLUSIONS: In COVID-19 patients without pre-existing diabetes, the presence of hyperglycaemia at admission is indicative of COVID-19-induced alterations in glucose metabolism and stress hyperglycaemia. Hyperglycaemia at admission in COVID-19 patients without diabetes is associated with an increased risk of invasive mechanical ventilation and in-hospital mortality. This finding highlights the importance for clinicians to carefully consider and select optimal support and treatment strategies for these patients. Further studies on the long-term consequences of hyperglycaemia in this specific population are warranted.

Kinetics of SuPAR hemoadsorption in critical COVID-19 patients on renal replacement therapy.

BACKGROUND: SARS-CoV-2 viral infection is associated with a rapid and vigorous systemic inflammatory response syndrome. Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker, both indicative of inflammation and propagating it. Hemoadsorption has been proposed as a potential therapy in COVID-19 patients, therefore the aim of this study is to determine suPAR kinetics during hemoadsoprtion. METHODS: This was a prospective observational study of critical COVID-19 patients, enrolled when hemoperfusion therapy was initiated. Hemoadsorber was integrated into the continuous renal replacement therapy circuit. The first series of suPAR measurements was performed 10 minutes after the start of the session, sampling both incoming and outgoing lines of the adsorber. A second series of the measurements was performed beforefinishing the session with the same adsorber. Statistical significance level was set < 0.05. RESULTS: This study included 18 patients. In the beginning of the session the fraction of suPAR cleared across the adsorber was 29.5% [16-41], and in the end of the session it decreased to 7.2% [4-22], 4 times lower, p = 0.003. The median length of session was 21 hours, with minimal duration of 16 hours and maximal duration of 24 hours. The median suPAR before the procedure was 8.71 [7.18-10.78] and after the session was 7.35 [6.53-11.28] ng/ml. There was no statistically significant difference in suPAR concentrations before and after the session (p = 0.831). CONCLUSIONS: This study concluded that in the beginning of the hemoadsorption procedure significant amount of suPAR is removed from the circulation. However, in the end of the procedure there is a substantial drop in adsorbed capacity. Furthermore, despite a substantial amount of suPAR cleared there is no significant difference in systemic suPAR concentrations before and after the hemoadsorption procedure.

Determinants of Increased Effort of Breathing in Non-Intubated Critical COVID-19 Patients.

Background and objectives: Acute respiratory distress syndrome (ARDS) is the most common complication occurring in COVID-19 patients admitted to the ICU. Given the increased respiratory work of these patients, it is necessary to evaluate their actual breathing efforts. The aim of this study is to report the incidence and determinants of increased effort of breathing (EOB) in critical COVID-19 patients. Materials and Methods: This was a retrospective study of COVID-19 patients admitted to the ICU during the year of 2020. Respiratory rate (RR) was chosen as an indicator of EOB. The cut-off value was set at more than 20 breaths per minute. ROC-AUC analysis was performed to identify the accuracy of the PaO2 and PaCO2 to determine increased EOB. Furthermore, multivariate regression analysis was performed to reveal the determinants of increased EOB. Results: 213 patients were included in the study. Mean RR in the population was 24.20 ± 6.28. 138 (64.8%) of the patients had increased EOB. The ROC-AUC analysis revealed the PaO2 (0.656 (CI 95%: 0.579−0.734, p < 0.001) as more accurate predictor of EOB than PaCO2 (0.584 (CI 95%: 0.505−0.662, p = 0.043). In the final multivariate model, the SpO2 (exp(B) = 0.922, CI 95%: 0.874−0.97 p = 0.033), PaO2/FiO2 ratio (exp(B) = 0.996, CI 95%: 0.922−1.000, p = 0.003) and PaO2 (exp(B) = 0.989 CI 95%: 0.982−0.996 p = 0.003) prevailed as independent predictors of increased EOB. Conclusions: To conclude, PaO2 was revealed as a more accurate predictor of increased EOB than PaCO2. Further investigation revealed the independent determinants of EOB: blood oxygen saturation, PaO2 and PaO2/FiO2 ratio.

VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).